Nitric oxide (NO) is a small, uncharged, highly reactive free radical that is synthesized from L-arginine by nitric oxide synthase (NOS) and may participate in acute and chronic lung injury. To help elucidate the role of NO in the pathogenesis of lung diseases, an animal model for NO- induced lung damage was developed. NO production was evaluated in male Sprague-Dawley rats after administration of either endotoxin or vehicle. Inducible NOS RNA was detected by Northern analysis, only in RNA extracted from lungs of animals injected with endotoxin but not in RNA from control animals. Alveolar macrophages isolated from lavage fluid of animals injected with endotoxin and cultured for 24 hours produced greater amounts of nitrite, an end-product of NO production, than did macrophages isolated from control animals. Nitrite was also found to be higher in lavage fluid from animals treated with endotoxin compared to lavage fluid from control animals. Morphologic evaluation of lung tissues showed inflammatory changes in animals injected with endotoxin.